Core D: Neuropathology Project Summary/Abstract Neuropathology is essential to identify the true causes of brain disease. Although biomarkers are increasingly valuable as harbingers of disease in presymptomatic stages, there remains a need to validate CSF and neuroimaging biomarkers. In the older brain, more than one disease often is at work and at present only a detailed neuropathologic examination can determine the presence of coexisting diseases which may contribute in complex ways to the progression to dementia. Thus, the Neuropathology Core is essential for the ADRC to achieve its stated goals. Specifically, The Neuropathology Core has the following aims: Aim 1: To make neuropathologic diagnoses on all new brain accessions from ADRC research participants using standard diagnostic criteria. Aim 2: To perform brain autopsies and to collect, store, and distribute formalin-fixed, paraffin-embedded, and frozen brain tissue samples to support ADRC projects and investigators and outside collaborations that enhance ADRC research goals. Aim 3: To develop and maintain a computerized neuropathology database (CaTissue) in concert with the Data Management and Biostatistics Core (Core C) and the Clinical Core (Core B). Another interaction of the Neuropathology Core with the Clinical Core is to work closely with the Clinical Core autopsy coordinator, who is instrumental in arranging autopsy permission and in making arrangements for the body once death has occurred. This includes transporting the body to WUSM for autopsy. Aim 4: To support Project 2 (Aim 3), Core D will provide clinically and neuropathologically well-characterized cases of AD with and without Lewy bodies to determine how Ab and a-synuclein compete for clearance pathways. Aim 5: To support Project 1 (Aim 2C) Core D will quantify the molecular pathology (tauopathy and b- amyloidosis) in those participants who have undergone 18F-T807tau and 18F-florbetapir amyloid imaging who have come to autopsy in order to correlate PET amyloid and tau data with lesion number and density in histological sections of brain-matched areas.